Effects of assisted reproductive technology on gene expression in heart and spleen tissues of adult offspring mouse

Abstract

ObjectivesAssisted reproductive technology (ART) is an important part of reproductive medicine, whose possible effects on offspring’s health have drawn widespread attention in recent years. However, relevant studies are limited to postnatal short-term follow-up and lack of diverse sample sources analysis other than blood.MethodsIn this study, a mouse model was used to explore the effects of ART on fetal development and gene expression in the organs of offspring in the adulthood using next-generation sequencing. The sequencing results were then analyzed.ResultsThe results showed that it caused abnormal expression in 1060 genes and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and the cardiovascular system development also shows enrichment. STRING analysis identified Ccl2, Ptgs2, Rock1, Mapk14, Agt, and Wnt5a as the core interacting factors. DEGs in the spleen are significantly enriched in anti-infection and immune responses, which include the core factors Fos, Jun and Il1r2. Further exploration revealed the abnormal expression of 42 and 5 epigenetic modifiers in the heart and spleen, respectively. The expression of the imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the hearts of ART offspring, and the DNA methylation levels of Igf2- and Mest-imprinting control regions (ICRs) increased abnormally.ConclusionIn the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring and that these changes are related to the aberrant expression of epigenetic regulators.

Cardiovascular health of offspring conceived by assisted reproduction technology: a comprehensive review

“…Further investigation revealed that 42 epigenetic modifiers were abnormally expressed in the heart. In addition, in the hearts of ART offspring, the expression of imprinted genes Dhcr7, Igf2, Mest, and Smoc1 was found to be reduced, whereas the DNA methylation levels of the Igf2- and Mest-imprinting control regions (ICRs) were abnormally increased ( 19 ). Superovulation in adult mice has also been linked to alterations in Sgce and Zfp777 imprinted genes, whereas in vitro culture of follicles from the early pre-antral stage resulted in globally reduced methylation and heightened variability at imprinted loci in blastocysts ( 48 ).…”

Up-regulated mRNA expression of VEGFA receptors (FLT1 and KDR) in placentas after assisted reproductive technology fertilization

“…Assisted reproductive technology (ART) has developed rapidly in recent years to support infertility treatment (Chen et al 2023). This technology is utilized during a critical period of gamete and embryo development at the time when the genome is undergoing signi cant epigenetic remodeling, and changes in the environment can easily affect normal developmental programming (Heber, Ptak 2021; Chen et al…”